穿心莲内酯三马来酸单酯的合成及其解热抗炎作用研究

 目的合成穿心莲内酯三马来酸单酯,并对其解热抗炎作用进行研究,以期发现活性较强的穿心莲内酯结构修饰物。方法以穿心莲内酯、马来酸酐为原料制备目标物。采用干酵母致大鼠发热、二硝基苯酚致大鼠发热及内毒素致家兔发热模型观察穿心莲内酯三马来酸单酯的解热作用;采用蛋清致大鼠足肿胀、大鼠棉球肉芽肿及二甲苯致小鼠腹膜炎模型观察抗炎作用。结果目标物结构经元素分析、质谱、核磁共振氢谱确证。其量效关系明显:300,150mg·kg^-1对干酵母和二硝基苯酚所致的大鼠发热及内毒素所致的家兔发热均有较好的解热作用,75 mg·kg^-1对3种发热作用均不明显;400,200 mg·kg^-1对蛋清所致的大鼠足肿胀、大鼠棉球肉芽肿及二甲苯所致的小鼠腹膜炎均有较好抗炎作用,100 mg·kg^-1对3种炎症作用均不明显。结论穿心莲内酯三马来酸单酯有较好的解热抗炎作用。

Studies on synthesis of andrographolide trimaleic acid monoester and its antipyretic and anti-inflammatory activity

OBJECTIVE To synthesize andrographolide trimaleic acid monoester(ATME) and study its antipyretic and anti-inflammatory activity. METHODS The target compound was prepared from andrographolide and maleic anhydride. The antipyretic activity of ATME was observed in rats with high temperature induced by dried yeast and 2,4-dinitrophenol, and in rabbits with high temperature induced by endotox-in, respectively.The anti-inflammatory activity was observed in rats with foot edema induced by egg white,rats with granulation edema induced by cotton ball and mice with peritonitis induced by xylene.RESULTS The target structure was identified by EA, MS and ¹H-NMR. ATME showed significant antipyretic activity in rats with high temperature induced by dried yeast and 2,4-dinitrophenol, and in rabbits with high temperature induced by endotoxin at the dose of 300,150 mg·kg^-1. ATME appeared significant anti-inflammatory activity in rats with foot edema induced by egg white, rats with granulation edema induced by cotton ball and mice with peritonitis induced by xylene at the dose of 400,200 mg·kg^-1.CONCLUSION ATME manifests obvious antipyretic and anti-inflamtory activity.